clear cell rcc
Recently Published Documents


TOTAL DOCUMENTS

111
(FIVE YEARS 38)

H-INDEX

7
(FIVE YEARS 2)

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S71-S71
Author(s):  
Y Wang ◽  
S Ganesan ◽  
R Rayes-Danan ◽  
S Williamson

Abstract Introduction/Objective The histologic features of renal cell carcinoma (RCC) after immunotherapy are not fully established. We report the pathologic findings of one case of clear cell RCC after treatment with pembrolizumab which is a humanized monoclonal anti-PD1 antibody. Methods/Case Report 46-year-old man completed three cycles of pembrolizumab for recurrent basal cell carcinoma. A 5.0 cm mass was incidentally found within left kidney during staging CT scan. He subsequently had left radical nephrectomy. Pathologic examination of nephrectomy specimen identified one 5.0 cm, well-circumscribed, solid mass in the upper pole, confined to the kidney with predominantly hemorrhagic, focally golden-yellow soft cut surface. The remaining parenchyma appears unremarkable. The pelvicalyceal system is not dilated. Sections of tumor show predominance of foamy histiocytes, lymphoplasmacytic infiltrate, and scattered cells having pale or eosinophilic cytoplasm, conspicuous nucleoli and low nuclear: cytoplasm ratio. Cholesterol clefts and hemosiderin deposits are noted. The immunostaining profile highlights areas suspicious for viable tumor cells by using pan-keratin, CK8/18, EMA, CA9 and CD10. Focal positivity in the same area is noted by the stains of PAX 8 and AMACR. However, with numerous histiocytes, it is difficult to determine if the tumor cells are positive for Vimentin. Moreover CD 117 is negative in the tumor cells. Results (if a Case Study enter NA) NA Conclusion Differential diagnosis includes renal cell carcinoma and xanthogranulomatous pyelonephritis. The overall findings support a clear cell RCC affected by the immunotherapy. With immunotherapy-based combinations becoming standard of care in advanced malignancies, it makes the pathological diagnosis more challenging and difficult, especially for incidental tumors.


Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4140
Author(s):  
Sai Krishnaraya Doppalapudi ◽  
Zev R. Leopold ◽  
Akshay Thaper ◽  
Alain Kaldany ◽  
Kevin Chua ◽  
...  

Patients with advanced or malignant renal cell carcinoma at the time of diagnosis have historically had a poor prognosis. Immunonologic agents have significantly altered the therapeutic landscape and clinical outcomes of these patients. In this review, we highlight recent and upcoming clinical trials investigating the role of immunotherapies in clear cell RCC. In particular, we emphasize immunotherapy-based combinations, including immune checkpoint inhibitor (ICI) combinations, neoadjuvant, and adjuvant ICI, and ICI agents combined with anti-VEGF therapy.


2021 ◽  
Vol 10 (33) ◽  
pp. 2718-2722
Author(s):  
Sarumathy Ganesan ◽  
Prathiba Arumugam ◽  
Nithya Ilanchezhian ◽  
Saraswathi Manickam

BACKGROUND Renal cell carcinoma (RCC) is the most common malignant renal tumour in adults. Prognosis of RCC depends on various factors like tumour stage, nuclear grade and histological type. For planning adjuvant therapy, accurate prediction of prognosis is mandatory. In many studies, ki67 and MUC1 has shown to be of prognostic significance and immunohistochemical expression of these two markers plays an important role in determining the prognosis of RCC. The purpose of this study was to evaluate the Ki67 expression in histologically confirmed cases of RCC and MUC1 expression in clear cell renal cell carcinoma, and to correlate them with the stage and Fuhrman nuclear grade of the tumour, in order to determine their role as prognostic markers in RCC. METHODS This study was a retrospective study. A total of 50 specimens of renal cell carcinoma were studied. The specimens were total and partial nephrectomy done in the department of urology for a period of 3 years. Expression of Ki67 and MUC1 in RCC were studied by immunohistochemistry (IHC). Statistical analysis was performed and P value < 0.05 was considered significant. RESULTS Out of 50 RCC studied, Ki67 labelling index ≥ 15 % was found in 35 cases. For MUC1, immunoreactivity of more than 10 % of tumor cell was found in 28/34 of clear cell RCC. In this study, Ki67 labelling index showed statistically significant expression with the stage of tumor and the nuclear grade. MUC1 expression also showed significant correlation with nuclear grade and stage of clear cell RCC. CONCLUSIONS High Ki67 labelling index in renal cell carcinoma is seen to correlate with higher nuclear grade and stage of tumor. High level expression with circumferential staining pattern of MUC1 is seen in high grade tumours with increased risk of metastasis. So MUC1 and Ki67 can be considered as a marker of prognosis of RCC. KEY WORDS Renal Cell Carcinoma, Immunohistochemistry, Ki67, MUC1


Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3807
Author(s):  
Pierangela Sepe ◽  
Arianna Ottini ◽  
Chiara Carlotta Pircher ◽  
Andrea Franza ◽  
Melanie Claps ◽  
...  

Non-clear cell renal cell carcinomas (RCC) comprise several rare and poorly described diseases, often characterized by bad prognosis and with no standard treatments available. The gap in their clinical management is linked to the poor molecular characterization in handling the treatment of non clear-cell RCC with untailored therapies. Due to their rarity, non-clear RCC are in fact under-represented in prospective randomized trials. Thus, treatment choices are based on extrapolating results from clear cell RCC trials, retrospective data, or case reports. Over the last two decades, various options have been considered as the mainstay for the treatment of metastatic RCC (mRCC), including angiogenesis inhibitors, vascular endothelial growth factor receptor inhibitors, other tyrosine kinase inhibitors (TKIs), as well as MET inhibitors and mammalian targeting of rapamycin (mTOR) inhibitors. More recently, the therapeutic armamentarium has been enriched with immunotherapy, alone or in combination with targeted agents that have been shown to significantly improve outcomes of mRCC patients, if compared to TKI single-agent. It has been widely proven that non-clear cell RCC is a morphologically and clinically distinct entity from its clear cell counterpart but more knowledge about its biology is certainly needed. Histology-specific collaborative trials are in fact now emerging to investigate different treatments for non-clear cell RCC. This review summarizes pathogenetic mechanisms of non-clear cell RCC, the evolution of treatment paradigms over the last few decades, with a focus on immunotherapy-based trials, and future potential treatment options.


2021 ◽  
Author(s):  
Sophie FERLICOT ◽  
Pierre-Alexandre Just ◽  
Eva Compérat ◽  
Etienne Rouleau ◽  
Frédérique Tissier ◽  
...  

Abstract Background: Hereditary papillary renal cell carcinoma (HPRCC) is a rare autosomal dominant disease characterized by the development of multiple and bilateral papillary type I renal cell carcinomas (RCC) and papillary adenomas caused by activating mutations in the MET proto-oncogene. Classically, distinctive histological features of RCC are described according to the familial renal cell carcinoma syndrome. To date, no clear cell RCC has been reported in HPRCC syndrome. Case presentation: We describe the case of a 51-year-old man with a germline MET mutation, who developed numerous papillary tumors but also unexpectedly clear cell renal cell carcinomas. During the follow-up, an adrenal metastasis was observed seven years after the initial diagnosis corresponding to a clear cell RCC metastasis. Using FISH, the metastatic tumor presented a trisomy of chromosomes 7 and 17. These genomic alterations are usually detected in papillary RCC, highlighting the potential link between both histological subtypes of tumors and the HPRCC syndrome.Conclusions: The pathologist must be aware that the presence of a non-papillary RCC associated with numerous papillary tumors should not exclude the diagnostic suspicion of HPRCC and thus to perform a thorough genomic study.


Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3652
Author(s):  
Kevin Zarrabi ◽  
Emily Walzer ◽  
Matthew Zibelman

Renal cell carcinoma (RCC) is a histologically heterogeneous disease with multiple subtypes. Clear cell RCC (ccRCC) represents the most common histology and has thus been easiest to study in clinical trials. Non-clear cell RCC (nccRCC) represents about 25% of RCC tumors, with fewer treatment options available, compared to ccRCC, and with poorer outcomes. Non-clear cell RCC tumors are histologically diverse, with each subtype having distinct molecular and clinical characteristics. Our understanding of nccRCC is evolving, with a gradual shift from treating nccRCC as a single entity to approaching each subtype as its own disease with unique features. Due to the scarcity of patients for study development, trials have predominantly combined all nccRCC subtypes and re-purposed drugs already approved for ccRCC, despite the decreased efficacy. We are now in the early stages of a potential paradigm shift in the treatment of nccRCC, with a rapid development of clinical studies with a focus on this subset of tumors. Investigators have launched trials focused on the molecular drivers of tumorigenesis using targeted therapies. Harboring the immunogenicity of some nccRCC subtypes, and based on promising retrospective studies, clinicians have also devised multiple trials using immune checkpoint inhibitors (ICIs), both alone or in combination with targeted therapies, for nccRCC subtypes. We highlight the promising completed and ongoing studies employing ICIs that will likely continue to improve outcomes in patients with nccRCC and propose future potential immunotherapeutic avenues.


2021 ◽  
Author(s):  
Γρηγόριος Θεοδωρόπουλος

Το φαινόμενο της επιθηλιομεσεγχυματικής μετατροπής είναι η διεργασία κατά την οποία ένα επιθηλιακό κύτταρο αποκτά φαινότυπο μεσεγχυματικού κυττάρου. Η μετατροπή αυτή στον φαινότυπο του επιθηλιακού κυττάρου απαιτεί την δημιουργία ενός νέου μοριακού προγράμματος του επιθηλιακού ιστού με νέες βιοχημικές οδηγίες. Η ΕΜΤ συμμετέχει σε φυσιολογικές καθώς και σε παθολογικές διεργασίες του οργανισμού. Σκοπό της παρούσας ερευνητικής δραστηριότητας αποτέλεσε η διερεύνηση της ανοσοιστοχημικής πρωτεινικής συνέκφρασης των μορίων ε-καντχερίνης και βιμεντίνης σε σειρά καρκινωμάτων νεφρού διάφορης ιστολογικής τυποποίησης και η συσχέτισή τους με τα κλινικοεργαστηριακά χαρακτηριστικά τους γνωρίσματα. Το υλικό αναδύθηκε από την αρχειακή ιστική βάση του Παθολογο-ανατομικού Τμήματος του Γενικού Νοσοκομείου Αθηνών ‘’ΕΛΠΙΣ’’ και αφορούσε σε - εμπεδωμένα σε κύβους παραφίνης – εκατό (n=100) σποραδικά πρωτοπαθή καρκινώματα νεφρού (RCC), προιόντα νεφρεκτομής. Παθολογοανατομικά ταξινομημένα σύμφωνα με τα ιστολογικά κριτήρια της WHO και όσον αφορά τη διαφοροποίηση βαθμονομημένα με το σύστημα κατά Furhman. Τα εξετασθέντα καρκινώματα αφορούσαν σε 75 διαυγοκυτταρικού τύπου (clear cell RCC), 13 θηλώδους τύπου (papillary RCC) και 12 χρωμόφοβου τύπου (chromophobe RCC). Σύμφωνα με τη συνδυασμένη συμβατική και ψηφιακή ανάλυση, υποέκφραση ή απώλεια της έκφρασης της ε-καντχερίνης παρατηρήθηκε σε 52 περιπτώσεις (52%), ενώ οι υπόλοιπες 48 (48%) χαρακτηρίστηκαν από μετρίου εώς ισχυρού βαθμού ανοσοέκφραση. Όσον αφορά τον ιστολογικό τύπο των εξετασθέντων περιστατικών, απώλεια της έκφρασης της ε-καντχερίνης συσχετίσθηκε περισσότερο με τα διαυγοκυτταρικά και θηλώδους τύπου (p=0.001). Ενδιαφέρουσα παρατήρηση αποτελεί ακόμη η προοδευτική απώλεια της έκφραση του μορίου σε σχέση με το βαθμό διαφοροποίησης του νεοπλάσματος κατά ταξινόμηση Fuhrman’s grade classification (p=0.002). Yποέκφραση ή απώλεια της έκφρασης της βιμεντίνης παρατηρήθηκε σε 19 περιπτώσεις (19%), ενώ οι υπόλοιπες 81 (81%) χαρακτηρίστηκαν από μετρίου εώς ισχυρού βαθμού ανοσοέκφραση. Όσον αφορά τον ιστολογικό τύπο των εξετασθέντων περιστατικών, απώλεια της έκφρασης της βιμεντίνης συσχετίσθηκε περισσότερο με τα διαυγοκυτταρικά και θηλώδους τύπου (p=0.001).


2021 ◽  
Vol 11 ◽  
Author(s):  
T. Anders Olsen ◽  
Dylan J. Martini ◽  
Subir Goyal ◽  
Yuan Liu ◽  
Sean T. Evans ◽  
...  

BackgroundImmune-checkpoint-inhibitors (ICIs) have become the cornerstone of metastatic renal-cell-carcinoma (mRCC) therapy. However, data are limited regarding clinical outcomes by race. In this study, we compared the real-world outcomes between African American (AA) and Caucasian mRCC patients treated with ICIs.MethodsWe performed a retrospective study of 198 patients with mRCC who received ICI at the Emory Winship Cancer Institute from 2015-2020. Clinical outcomes were measured by overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) defined as a complete or partial response maintained for at least 6 months per response evaluation criteria in solid tumors version 1.1. Univariate and multivariable analyses were carried out for OS and PFS by Cox proportional-hazard model and ORR by logistical-regression model. Descriptive statistics compared rates of immune-related adverse events (irAEs) and non-clear-cell-RCC (nccRCC) histology were assessed using Chi-square test.ResultsOur cohort was comprised of 38 AA and 160 Caucasian patients. Most were diagnosed with clear-cell-RCC (ccRCC) (78%) and more than half received (57%) PD-1/PD-L1 monotherapy. Most patients were intermediate or poor-risk groups (83%). Comparing to Caucasians, our AA cohort contained more females and nccRCC cases. Kaplan-Meier method showed AAs had no statistically different median OS (17 vs 25 months, p=0.368) and PFS (3.1 vs 4.4 months, p=0.068) relative to Caucasian patients. On multivariable analysis, AA patients had significantly shorter PFS (HR=1.52, 95% CI: 1.01-2.3, p=0.045), similar ORR (OR=1.04, 95% CI: 0.42-2.57, p=0.936) and comparable OS (HR=1.09, 95% CI: 0.61-1.95, p=0.778) relative to Caucasians.ConclusionsOur real-world analysis of ICI-treated mRCC patients showed that AAs experienced shorter PFS but similar OS relative to Caucasians. This similarity in survival outcomes is reassuring for the use of ICI amongst real-world patient populations, however, the difference in treatment response is poorly represented in early outcomes data from clinical trials. Thus, the literature requires larger prospective studies to validate these findings.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4580-4580
Author(s):  
Deepak Kilari ◽  
Aniko Szabo ◽  
Pooja Ghatalia ◽  
Tracy L Rose ◽  
Nicole Weise ◽  
...  

4580 Background: Despite advances in the treatment of clear cell RCC, there is a paucity of data to guide management of nccRCC due to the heterogeneity and rarity of these tumors. The clinical activity of new combination therapies (including immunotherapy (IO), anti-vascular endothelial growth factor inhibitors (VEGF), and mammalian target of rapamycin (mTOR) inhibitors) in metastatic nccRCC is not known. Methods: In this multicenter retrospective analysis, we explored the efficacy of combination systemic therapies in patients with nccRCC. Baseline and follow-up demographic, clinical, treatment, and radiographic data were collected. The primary endpoint was objective response rate (ORR) assessed by investigator review. Secondary endpoints include progression- free survival (PFS), disease control rate (DCR), median duration of response (DOR), overall survival (OS), and biomarker correlates. Results: Among 66 included patients, median age was 59 yr; 60% were male and 62% white. Histologies included papillary (38%), chromophobe (17%), unclassified (24%), translocation (12%), and other (9 %). Sarcomatoid and/or rhabdoid differentiation was present in 18%, 70% had prior nephrectomy, 86% were IMDC intermediate/poor risk, 29% and 32% had liver and bone metastasis respectively. 67% received combination treatment in the first line. Comparison of outcomes based on treatment regimen is shown in the table. Conclusions: Antitumor activity was observed with novel combinations in nccRCC which warrants further prospective studies. Response rates and survival with combination therapy in this dataset remain inferior to rates seen in clear cell RCC.[Table: see text]


Sign in / Sign up

Export Citation Format

Share Document